This is a request for five years of funding through the K25 Quantitative Mentored Research Career Development Award mechanism. The candidate, an imaging physicist and statistician, has proposed an intensive training and research program to facilitate her growth as an interdisciplinary scientist, capable of obtaining support for the development of newly emerging functional magnetic resonance imaging (fMRI) techniques to study substance abuse problems. The training plan reflects a combination of coursework, laboratory visits, and meetings to provide formal training in the areas of neuroscience and substance abuse that will both complement the experience of and expedite the successful completion of the research projects. The use of fMRI to study drug abuse problems is still relatively uncommon, but in general, holds great promise for this application, fMRI methods - both study designs and data/statistical analyses - are still evolving at a very rapid pace;this can be an incredible obstacle for investigators who wish to utilize fMRI but do not have the imaging background to select an appropriate study design. The research plan focuses on the optimization of novel fMRI techniques to study aspects of marijuana use in adolescents and adults and on the dissemination of these lesser known, yet incredibly flexible, methods to the substance abuse research community. The first project investigates differences in reactivity to visual, audio, and olfactory drug cues between adolescents and adults who use marijuana. Subjective responses (self-reports of cue-induced marijuana craving) and physiological responses (skin temperature, heart rate, and skin conductance) will be recorded and analyzed using multivariate statistical methods. Responses for both groups will also be compared with responses from healthy matched control subjects. The second project is an event-related fMRI study of the effects of cue induced craving on performance of an oddball task in adolescent and adult marijuana users (healthy matched control subjects will also be tested). The study design and data analysis strategy will permit the assessment of two different aspects of craving, each over a different time scale. The third project is a pharmacological fMRI (phMRI) study that will tackle the question of how acute administration of marijuana effects brain activity in adult marijuana users. The phMRI methods will be optimized to balance the impact of the unwieldy pharmacokinetic properties of marijuana and the small and temporally variable cognitive effects. All together, these three projects will constitute an invaluable training experience for the candidate while demonstrating the versatility of newer fMRI techniques in studying substance abuse problems and providing a better understanding of marijuana effects in adolescents and adults.